Temporal Window of Metabolic Brain Vulnerability to Concussion

OBJECTIVE: In the present study, the occurrence of the temporal window of brain vulnerability was evaluated in concussed athletes by measuring N-acetylaspartate (NAA) using proton magnetic resonance (H-MR) spectroscopy. METHODS: Thirteen nonprofessional athletes who had a sport-related concussive head injury were examined for NAA determination by means of H-MR spectroscopy at 3, 15, and 30 days postinjury. All athletes but three suspended their physical activity. Those who continued their training had a second concussive event and underwent further examination at 45 days from the initial injury. The single case of one professional boxer, who was studied before the match and 4, 7, 15, and 30 days after a knockout, is also presented. Before each magnetic resonance examination, patients were asked for symptoms of mild traumatic brain injury, including physical, cognitive, emotional, and sleep disturbances. Data for H-MR spectroscopy recorded in five normal, age-matched, control volunteers, who were previously screened to exclude previous head injuries, were used for comparison. Semiquantitative analysis of NAA relative to creatine (Cr)- and choline (Cho)-containing compounds was performed from proton spectra obtained with a 3-T magnetic resonance system. RESULTS: Regarding the values of the NAA-to-Cr ratio (2.21 +/- 0.11) recorded in control patients, singly concussed athletes, at 3 days after the concussion, showed a decrease of 18.5% (1.80 +/- 0.04; P < 0.001). Only a modest 3% recovery was observed at 15 days (1.88 +/- 0.1; P < 0.001); at 30 days postinjury, the NAA-to-Cr ratio was 2.15 +/- 0.1, revealing full metabolic recovery with values not significantly different from those of control patients. These patients declared complete resolution of symptoms at the time of the 3-day study. The three patients who had a second concussive injury before the 15-day study showed an identical decrease of the NAA-to-Cr ratio at 3 days (1.78 +/- 0.08); however, at 15 days after the second injury, a further diminution of the NAA-to-Cr ratio occurred (1.72 +/- 0.07; P < 0.05 with respect to singly concussed athletes). At 30 days, the NAA-to-Cr ratio was 1.82 +/- 0.1, and at 45 days postinjury, the NAA-to-Cr ratio showed complete recovery (2.07 +/- 0.1; not significant with respect to control patients). This group of patients declared a complete resolution of symptoms at the time of the 30-day study. CONCLUSION: Results of this pilot study carried out in a cohort of singly and doubly concussed athletes, examined by H-MR spectroscopy for their NAA cerebral content at different time points after concussive events, demonstrate that also in humans, concussion opens a temporal window of brain metabolic imbalance, the closure of which does not coincide with resolution of clinical symptoms. The recovery of brain metabolism is not linearly related to time. A second concussive event prolonged the time of NAA normalization by 15 days. Although needing confirmation in a larger group of patients, these results show that NAA measurement by H-MR spectroscopy is a valid tool in assessing the full cerebral metabolic recovery after concussion, thereby suggesting its use in helping to decide when to allow athletes to return to play after a mild traumatic brain injury.